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The genetic landscape of mutations in Burkitt lymphoma

Abstract

Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34% of Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a new tumor suppressor gene.

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Figure 1: Results from whole-genome sequencing of a Burkitt lymphoma tumor and germline DNA.
Figure 2: Exome sequencing in Burkitt lymphoma.
Figure 3: Patterns of exonic mutations in Burkitt lymphoma compared to DLBCL.
Figure 4: Recurrent ID3 mutations in Burkitt lymphomas.

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Acknowledgements

The authors thank S. Sunay and the Georgia Cancer Coalition for support in sample collection. A.B.M. was supported by the Hertz Foundation. This work was supported through grants R21CA1561686 and R01CA136895 from the National Cancer Institute (S.S.D.). S.S.D. was also supported by the American Cancer Society. We gratefully acknowledge the generous support of C. Stiefel and D. Stiefel.

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Authors and Affiliations

Authors

Contributions

C.L., R.M., K.L.R., C.H.D., W.W.L.C., G.S., P.L.L., D.A.R., A.S.L., L.B.-M., K.P.M., C.R.F., K.N.N., A.M.E., A.C., L.I.G., M.B.C., J.I.G., E.D.H., J.Z., G.L., A.G., M.M., S.L. and S.S.D. performed research and edited the manuscript. C.L., J.Z., A.B.M., D.J., Z.S., V.G., A.B., D.B.D. and S.S.D. analyzed data. C.L. and S.S.D. wrote the manuscript.

Corresponding author

Correspondence to Sandeep S Dave.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Note and Supplementary Figures 1–10 (PDF 4090 kb)

Supplementary Table 1

Burkitt lymphoma whole genome sequencing variants (XLS 2765 kb)

Supplementary Table 2

Sanger sequence validation (XLS 66 kb)

Supplementary Table 3

Recurrently mutated genes in Burkitt lymphoma (XLS 50 kb)

Supplementary Table 4

Individual variants found in Burkitt lymphoma (XLS 217 kb)

Supplementary Table 5

Patient data (XLS 42 kb)

Supplementary Table 6

Primer sequences (XLS 30 kb)

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Love, C., Sun, Z., Jima, D. et al. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet 44, 1321–1325 (2012). https://doi.org/10.1038/ng.2468

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